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Biomedical subjects

M E Arlot

Publications and source records attributed to M E Arlot.

13 recordsLinked to original sources
PubMed1992

Vitamin D3 and calcium to prevent hip fractures in elderly women.

BACKGROUND: Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. METHODS: We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. RESULTS: Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001). CONCLUSIONS: Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Aged↗
PubMed1992

Treatment of osteoporosis with parathyroid peptide (hPTH 1-34) and oestrogen: increase in volumetric density of iliac cancellous bone may depend on reduced trabecular spacing as well as increased thickness of packets of newly formed bone.

OBJECTIVE: We wished to determine whether treatment of vertebral osteoporosis with human parathyroid peptide 1-34 (hPTH 1-34), given as a daily injection with supplementary treatment with hormone replacement therapy (HRT), increases cancellous bone area in the ilium by increasing the size of packets of new bone. DESIGN AND MEASUREMENTS: The width of packets of cancellous bone (wall width) was measured at random intercepts and mean values calculated. Cancellous bone area and perimeter were also measured. Indices of trabecular separation and the complementary quantity trabecular number were derived according to Parfitt's method, as well as trabecular width. Patients were used as their own controls and changes in these indices calculated. Correlations were calculated for data obtained from independent measurements. PATIENTS: We studied eleven women with post-menopausal osteoporosis, diagnosed by fractures after exclusion of causes of secondary osteoporosis. RESULTS: One woman did not comply with her HRT therapy. In the others, treatment with hPTH 1-34 + HRT restored the characteristically depressed pre-treatment values of wall width to normal. Trabecular width increased approximately four times more than wall width. Changes in wall width correlated with changes in cancellous bone area; however, bone area increased considerably more than could be accounted for statistically by changes in wall width. A decrease in trabecular separation was found to account for the additional increase in bone area (P = 0.056). CONCLUSION: hPTH 1-34 + oestrogen and progestagen therapy increases the width of packets of new cancellous bone with consequent increases in the width of trabecular plates.

Aged↗
PubMed1992

Serum osteocalcin is increased in patients with osteomalacia: correlations with biochemical and histomorphometric findings.

The synthesis of osteocalcin or bone gla protein by osteoblasts is markedly stimulated by 1,25-(OH)2D, a key hormone in the regulation of bone mineralization. The circulating levels of osteocalcin have been shown to reflect both the osteoid matrix production and the formation rate of mineralized bone in several metabolic bone diseases (osteoporosis, thyrotoxicosis, primary hyperparathyroidism) in which both mechanisms are tightly coupled because of the absence of mineralization defect. In this study, we measured in 12 patients (7 women, 5 men, 56 +/- 15 yr old) with untreated osteomalacia serum osteocalcin and vitamin D metabolites (25OHD and 1,25-(OH)2D). The results were correlated with biochemical and histomorphometric assessment of bone remodeling. Osteomalacia was due to vitamin D deficiency (5 cases), to vitamin D malabsorption (6 cases), and to hypophosphataemia in 1 case. When compared to control values, serum osteocalcin was increased in patients with osteomalacia (7.4 +/- 4 vs. 3.7 +/- 1.3 ng/mL; P less than 0.001) and was positively correlated with serum alkaline phosphatase (r = 0.65; P = 0.03) and negatively with 25 OHD (r = -0.61; P = 0.04). Serum osteocalcin was not correlated with 1,25-(OH)2D [r = -0.45; not significant (NS)] even after exclusion of the patient with hypophosphataemia. Serum osteocalcin was positively correlated with the osteoid volume and osteoid perimeter (r = 0.71 and 0.69 respectively; P less than 0.01) but not with any of the tetracycline-based parameter of bone mineralization at the tissue level (r ranging from -0.41 to +0.42, NS). Serum 25 OHD, but not 1,25-(OH)2D, was positively correlated with the mineralization rate (r = 0.59; P less than 0.05 and r = 0.54; NS). We conclude that in patients with osteomalacia, a condition which is characterized by an increased osteoid accumulation due to a decreased mineralization rate, the increased level of serum osteocalcin reflects the increased osteoid synthesis but not the mineralization defect. In this disease, serum osteocalcin is inversely correlated to the severity of vitamin D deficiency reflected by serum 25 OHD, but not to the serum levels of 1,25-(OH)2D.

Adult↗
PubMed1991

Iliac trabecular bone formation predicts radial trabecular bone density changes in type 1 osteoporosis.

In 28 patients with idiopathic or postmenopausal type 1 (spinal crush fracture) osteoporosis, resorption indices and dynamic measurements of trabecular bone formation based on in vivo tetracycline labeling in 7.5 mm transiliac biopsies have been compared with trends in radial cortical and trabecular bone density measured with computed tomography. Positive correlations were observed between trabecular bone density trends in the radius and indices of bone formation in the ilium. These were improved when one of the two resorption indices was included with a formation index in bivariate regressions. Marked interindividual variations in radial bone density trends were also seen in cortical bone. These correlated poorly with trends in trabecular bone. Weak negative relationships between cortical bone trends and indices relating to bone formation and resorption were observed, but a positive association was seen with single-labeled surfaces on iliac trabeculae. If, as has been suggested, there are periodic variations in bone formation, the results suggest that axial and peripheral trabecular bone density trends are synchronized in osteoporosis, perhaps in response to systemic factors, such as circulating hormones.

Aged↗
PubMed1991

The relationship between serum vitamin D concentrations and in vivo tetracycline labeling of osteoid in crush fracture osteoporosis.

Twenty of 22 consecutive British patients with crush fracture osteoporosis had transiliac bone biopsies following double in vivo tetracycline labeling synchronized with the collection of serum for the measurement of vitamin D metabolites. A significant but direct (rather than inverse) relationship was found between 25-hydroxyvitamin D (calcidiol) levels and the fraction of cancellous surfaces covered with osteoid not taking either tetracycline label (r = 0.53, P less than 0.02). There was no correlation with 1,25-dihydroxyvitamin D levels. No patient had frankly thickened osteoid seams although 3 had reduced but measurable calcidiol levels. These results make it unlikely that the majority of patients with osteoporosis who have osteoid of normal thickness but reduced uptake of tetracycline have a mineralization defect secondary to vitamin D deficiency. The pathophysiological significance of unlabeled osteoid in osteoporosis requires further investigation.

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PubMed1990

Trabecular and endocortical bone remodeling in postmenopausal osteoporosis: comparison with normal postmenopausal women.

To assess the bone turnover abnormalities which characterize postmenopausal osteoporosis with vertebral fractures (PMOp), a transiliac bone biopsy was performed after double labeling of the mineralizing front with tetracycline in 50 untreated PMOp patients who were compared with 13 healthy age-matched volunteer females. The analysis of bone remodeling and structure parameters demonstrated that PMOp is a disease affecting both the cancellous and the endocortical envelopes and characterized by increased resorption and by a marked decrease in the osteoblastic apposition rate due to a reduced duration of bone formation. This induces a decrease in the width of both individual osteons and trabeculae. In PMOp, the wide spectrum of bone turnover as compared with the controls, associated with the typical bimodal distribution of cancellous osteoid perimeter, allowed us to identify two subsets, one with normal turnover (NT) and one with high turnover (HT) representing 30% of the cases. When compared to NT, HT was characterized by increased osteoclast number, lower bone volume, thinner osteons, increased formation at the tissue-level and markedly decreased duration of formation. In HT the marked decrease in the duration of activity of osteoblasts and the markedly increased number of osteoclasts induced a greater decrease in bone volume, despite the increase of bone formation at the tissue level. These subsets could not be distinguished by any clinical or biochemical parameter except for serum bone gla protein (osteocalcin) which was significantly higher (as a group) in HT than in NT. The underlying cause for these two subsets is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1987

The assessment of bone formation and bone resorption in osteoporosis: a comparison between tetracycline-based iliac histomorphometry and whole body 85Sr kinetics.

Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption. The idea that continued bone loss in some patients is associated with defective osteoblastic bone formation is supported by the low rates found in some patients by both techniques. Heuristically these studies validate both in vivo tetracycline labeling for dynamic histomorphometry and corrections for long-term exchange in kinetic studies of bone formation, providing a quantitative framework for the design and analysis of future studies of bone remodeling in the osteoporoses.

Adult↗
PubMed1987

Coherence treatment of postmenopausal osteoporosis with growth hormone and calcitonin.

Fourteen women with postmenopausal osteoporosis, all having at least one vertebral crush fracture, were randomly assigned to two treatment arms, each lasting 24 months. The coherence treatment group (7 patients) was treated in the following sequence: human growth hormone (hGH) 7 IU subcutaneously daily for 2 months, followed by 3 months of salmon calcitonin (CT), 100 MRC units every other day. After a 3 month rest period, this sequence was repeated twice. The contrast group (7 patients) was treated intermittently with salmon CT given in the same time periods and at the same dose as in the coherence treatment group. Bone mass was measured every 4 months by neutron activation analysis for total body calcium (TBCa) and by single photon absorptiometry for bone mineral content (BMC) of the distal radius. Although there were no significant differences between the two groups (two-way ANOVA), the rate of change in TBCa in the coherence treatment group was significantly different from zero (F = 3.8, P less than .05) and was +2.3%/year. The increase in bone mass appeared to be sustained throughout the 2 year study, in contrast with previous studies where a plateau effect was observed with calcitonin given alone or continuously with growth hormone. No significant change was found in bone histomorphometric values measured before and after treatment in 4 patients from each group.

Aged↗
PubMed1985

Intersample variation in bone histomorphometry: comparison between parameter values measured on two contiguous transiliac bone biopsies.

In order to evaluate the intersample variations for bone histomorphometric parameters in various metabolic bone diseases, either for a group or for one single patient, two complete contiguous transiliac bone biopsies were taken in 55 subjects. The diagnoses were osteoporosis (OP), renal osteodystrophy (ROD), osteomalacia (OM), primary hyperparathyroidism (HPT), metastatic bone disease, fluorosis, thyrotoxic bone, and "normal" bone. The following histomorphometric parameters were measured: trabecular bone volume (TBV), trabecular osteoid surfaces (TOS) and volume (TOV), trabecular resorption surfaces (TRS), and calcification rate (CR). The thickness index of osteoid seams (TIOS) was calculated. The measurements were performed with both manual and computerized methods which give similar results according to our previous study. The differences between parameters values measured on both cores were expressed by the difference in percent of the mean and by the intrapair coefficient of variation. Moreover, for each parameter, the confidence interval for one subject was calculated from the residual mean square of a two-way analysis of variance. For each parameter, the intersample variation differs according to the diagnosis. Confidence interval (risk = 5%) for one single subject reaches 29% for TBV in OP; 16% for TOS; 26% for TOV and TIOS in OM; 25% for TRS in ROD, and 69% in HPT, but is much lower for groups of 10 and 20 patients. These variations must be taken into account when successive biopsies are performed in one individual or in groups of patients to follow the course of a disease or evaluate the effects of a therapy.

Adolescent↗
PubMed1985

Intermethod variation in bone histomorphometry: comparison between manual and computerized methods applied to iliac bone biopsies.

The intermethod variation in the measurement of basic bone histomorphometric parameters was evaluated on 100 undecalcified transiliac bone biopsies. Two contiguous samples were taken from 50 patients (33 females; 17 males; mean age: 52 +/- 19 years) for diagnostic purposes. The diagnoses were osteoporosis (n = 38), renal osteodystrophy (n = 18), primary hyperparathyroidism (n = 16), osteomalacia (n = 12), metastatic bone disease (n = 2), thyrotoxic bone (n = 2), fluorosis (n = 2), and 10 biopsies were considered as "normal" bone. Trabecular bone volume (TBV) was measured with both a manual integrating eyepiece and an automatic (QUANTIMET 720-Cambridge Instruments, Cambridge, England) method. Trabecular resorption surfaces (TRS), trabecular osteoid surfaces (TOS), and volume (TOV) were measured with both a manual and a semiautomatic (VIDEOPLAN-Kontron, Munich, West Germany) method. The calcification rate (CR) was measured with both a manual and a semiautomatic method in eight cases after double labeling with tetracycline. Inter- and intraobserver variations were always lower with the automatic and semiautomatic methods than with the manual method, except for TOV. For all the parameters there was a highly significant correlation between manual and computerized methods (0.98 greater than r greater than 0.90). For TBV and CR no significant difference was noted, but for TBV the QUANTIMET appeared more sensitive, that is, better able to detect low values of the structure to be measured. For TRS, the manual method underestimated low values and appeared less sensitive than the semiautomatic method. For the 100 biopsies, the VIDEOPLAN underestimated the osteoid parameters by 13% for TOS and 26% for TOV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Bone histology in adults with aseptic necrosis. Histomorphometric evaluation of iliac biopsies in seventy-seven patients.

UNLABELLED: We studied the bone histology by histomorphometric methods in transiliac bone-biopsy specimens from seventy-seven adult patients with aseptic osteonecrosis and normal kidney function. The trabecular bone volume, trabecular osteoid volume, trabecular osteoid surfaces, thickness index of osteoid seams, total resorption surfaces, calcification rate, tetracycline-labeled surfaces, and bone-formation rate at the basic multicellular unit level and at the tissue level were determined. Histological evidence of osteomalacia was found in nine patients, of whom four were alcoholics. In the remaining sixty-eight patients--fifteen treated with corticosteroids, twenty-nine alcoholics, and twenty-four who did not have any detectable etiological factor--a common histomorphometric profile was found. This consisted morphologically of a reduction in trabecular bone volume and in the thickness of osteoid seams, and dynamically of a reduction in calcification rate and in total labeled surfaces. All of these changes suggested a marked decrease in osteoblastic appositional rate and in bone-formation rate at the cell and tissue levels. This could induce a healing defect of microfractures and thus facilitate subchondral fractures. CLINICAL RELEVANCE: This histological study indicated that non-apparent bone disease--either osteoporosis or osteomalacia--may underlie aseptic osteonecrosis in almost all patients, and be found even when blood and urinary biochemical parameters, usually reflecting bone-remodeling, are normal. An iliac-crest bone biopsy with static and dynamic histomorphometric study is the appropriate method for detecting these abnormalities. These results are of importance for understanding the pathophysiological mechanisms underlying osteonecrosis as well as its prevention and treatment.

Adult↗
PubMed1981

Effects of two diphosphonates (EHDP and Cl2MDP) on serum uric acid in pagetic patients.

The effects on serum uric acid (SUA) of two diphosphonates (EHDP at 5 and 20 mg/kg/day and Cl2MDP at 400 and 1600 mg/day) were studied in 49 pagetic patients treated for 6 months. Patients were divided into two groups: group I, initially normouricemic (SUA less than 385 mumol/l); group II, initially hyperuricemic (SUA greater than or equal to 385 mumol/l). SUA was significantly decreased (P less than 0.01) after 6 months of diphosphonate therapy in all group II patients. However, 3 months after withdrawal of therapy, SUA returned to values not significantly different from those initially recorded in this group. SUA did not change during or after treatment in the group I patients. Groups I and II could not be differentiated on the basis of initial serum alkaline phosphatase or urinary hydroxyproline values. In response to therapy, both groups showed the same reduction in these parameters. These results suggest that diphosphonates have no effect at a single level in uric acid metabolism. They certainly reduce the part of the urate pool coming from the nucleic acids of the increased bone cell population by reducing the number of osteoclasts and osteoblasts, which is extremely high in pagetic bone. They also must act on uric acid metabolism through other mechanisms which need to be investigated in further studies.

Adult↗